Apoptosis is an active biological process of elimination, by fragmentation, of certain cells of the organism.
It constitutes a programmed elimination of cells at the biological tissue level, under genetic control. The elimination may be natural (surplus cells in the tissue) or induced by various forms of stress.
The biological cascade of apoptosis is known and uses a number of effectors such as caspases, in particular the effector caspases 3 or 7, which will implement the apoptosis programme, and the initiating caspases 8 and/or 9, which will trigger it.
A certain number of apoptosis inhibitors are also known (Deveraux et al., Genes Dev. 13 (1999), pp. 239-252), among which is survivin. These inhibitors therefore regulate cell survival, thus participating in cell homeostatis in biological tissues.
Survivin, the only member of the IAP (Inhibitor of Apoptosis Protein) family, is a bifunctional protein capable both of balancing the apoptosis of cells and of regulating the cell cycle thereof.
Survivin inhibits in particular the activation of certain caspases, in particular caspases 3, 7 and 9.
This protein is expressed in strongly growing embryonic tissues, but is not expressed in adult differentiated tissues, except in tissues that have a physiological cell renewal and/or are involved in a repair process. Thus, at the cutaneous level, it is most particularly expressed in the keratinocytes of the basal layer of the epidermis, which provide formation and renewal of the latter.
It is in this basal layer that the epidermal stem keratinocytes are found, these being cells with a high potential for regeneration of this tissue, which have been demonstrated to be the most effective in forming a complete epidermis (J L Xie et al., J Plast Reconstr. Aesthet. Surg. 2007; 60(9); 983-90).
Now, it has been shown that survivin is mainly expressed in the stem cells of the epidermis (Marconi A, Dallaglio K, Lotti R, Vaschieri C, Truzzi F, Fantini F, Pincelli C, Stem cells 2007: 25: 149-155).
Conversely, overexpression of survivin shows a significant decrease in the number of apoptotic cells in the epidermis after exposure to ultraviolet radiation (Grossman et al., 2001 J Clin Invest 108; 991-999).
It has also been demonstrated that the inactivation of beta-1 integrins completely abolishes the cellular expression of survivin (Marconi A et al., Stem cells 2007: 25: 149-155) and leads the cells to apoptosis.
Beta-1integrins are adhesion proteins through which the keratinocytes of the epidermal basal layer adhere to the proteins of the dermal-epidermal junction.
Beta-1integrins are expressed more strongly by the stem cells of the epidermis (P. Jones, Cell 1993, 73: 713-724, Kaur J Invest Dermatol 2006, 126, 1450-1458), which corroborates the observation of a stronger expression of survivin in these cells.
Now, during ageing, a drop in the expression of beta-1 integrins in the keratinocytes (B Le Varlet et al. J Investig Dermatol Symp Proc. 1998, 3; 172-179) and in the wrinkled skin areas exposed to light (S Bosset et al. British J Dermatol 2003, 148; 7770-778) is observed.
Thus, the proteins which ensure maintenance of survivin in the basal cells of the epidermis decrease with age, and, in parallel, an increase in the sensitivity of the cells to apoptosis and a decrease in cycling cells are observed (Zuliani et al., J. Invest. Dermatol. 2004, 123:2, A50, 302), these observations converging to indicate a probable survivin deficiency in ageing skin.
In addition to its apoptosis-regulating role, survivin has been identified as a constituent of the “chromosomal passenger complex” which coordinates the chromosomes with the cytoskeleton during mitosis (Vader et al., EMBO reports, 2006, 7, 1, 85-92); it therefore plays an essential role in normal cell division, this division being impaired during ageing with, as a consequence, less renewal of the epidermis, thinning thereof, and the development of wrinkles.
Survivin is therefore a regulator of the survival and of the resistance of keratinocytes; it acts by modulating the sensitivity of apoptosis of the keratinocytes located in the basal layer of the epidermis, including the stem cells. It also regulates their capacity for renewal and for regeneration of the epidermis.
It thus makes it possible to spare the cell stock of the epidermis and to maintain efficient epidermal cell renewal.
Document WO 2006/069192 (GILLETTE Co) discloses the use, in cosmetics, of survivin-inhibiting agents for a hair and body-hair growth reduction effect.
To date, no compounds that act as survivin-expression stimulators have been described for uses in cosmetics.
As regards the plant of the Lepechinia genus, said genus comprises approximately 40 species, among which is Lepechinia caulescens, which are essentially found in Mexico and South America.
Lepechinia caulescens (Syn: Horminum caulescens Ortega), one of these species, is an erect perennial low plant 30 to 80 cm in height, the vegetative cycle of which is seasonally dependent, and which is found in Mexico, Nicaragua and Guatemala at altitudes between 1200 and 3900 m. Lepechinia caulescens is a species recognized in traditional medicine, in particular for its activity on diarrhoea and vomiting.
Published data exist on studies aimed at isolating chemical compounds present in these plants.
Di- and triterpenoid acids have been isolated from above-ground parts of Lepechinia caulescens (Delgado et al., Phytochemistry, 1994, 37 (4), 1119-21).
Some authors have demonstrated the vasorelaxing activity of a methanolic extract of Lepechinia caulescens, said activity being mediated by the presence of oleanolic acid and ursolic acid, which are two triterpenoic acids isolated from this plant.
Other authors have demonstrated, on an ileum isolated from rat, the spasmolytic activity of an organic extract obtained from the whole plant of the species Lepechinia caulescens, confirming experimentally the traditional use of the plant by local Mexican populations (Rodriguez-Lopez et al., Fitoterapia, 2003 74 725-728).
Some authors have also characterized an insulinomimetic activity of an organic extract of this plant (Roman et al, Arch. Med. Res. (Mex.), 1992; 23 105).
More recently, document U.S. Pat. No. 6,265,370 has described the use of fresh or dried flowers of Lepechinia in pulverized form, as a scented agent in a method for making soap.
However, to date, no data exist concerning the use of a plant species of the Lepechinia genus, in the form of the product of any method of extraction, as an active agent in cosmetic compositions.